The Effects of Bifidobacterium-based Probiotics in Reducing Blood Pressure in Middle-aged Chinese With Hypertension

Summary

The primary objective of this study is to investigate if a Bifidobacterium-based probiotic intervention would reduce clinic systolic BP in untreated middle-aged Chinese men and women with hypertension according to ACC/AHA guidelines (SBP ≥130 mm Hg) after 12 weeks of treatment. The investigators anticipate that this feasibility study will provide rationale to conduct a larger randomized clinical trial and preliminary data to estimate the power/ sample size of a larger RCT.

Timeline

Start

2026-05

Primary completion

2027-05

Completion

2027-05

Publications

• Background Chumpitazi BP, Self MM, Czyzewski DI, Cejka S, Swank PR, Shulman RJ. Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations. Neurogastroenterol Motil. 2016 Mar;28(3):443-8. doi: 10.1111/nmo.12738. Epub 2015 Dec 21.
• Background Kolodziejczyk AA, Zheng D, Elinav E. Diet-microbiota interactions and personalized nutrition. Nat Rev Microbiol. 2019 Dec;17(12):742-753. doi: 10.1038/s41579-019-0256-8. Epub 2019 Sep 20.
• Background Azzi A. Oxidative Stress: What Is It? Can It Be Measured? Where Is It Located? Can It Be Good or Bad? Can It Be Prevented? Can It Be Cured? Antioxidants (Basel). 2022 Jul 23;11(8):1431. doi: 10.3390/antiox11081431.
• Background Okita Y, Nakamura H, Kouda K, Takahashi I, Takaoka T, Kimura M, Sugiura T. Effects of vegetable containing gamma-aminobutyric acid on the cardiac autonomic nervous system in healthy young people. J Physiol Anthropol. 2009;28(3):101-7. doi: 10.2114/jpa2.28.101.
• Background Hayakawa K, Kimura M, Kamata K. Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. Eur J Pharmacol. 2002 Mar 1;438(1-2):107-13. doi: 10.1016/s0014-2999(02)01294-3.
• Background Verhaar BJH, Prodan A, Nieuwdorp M, Muller M. Gut Microbiota in Hypertension and Atherosclerosis: A Review. Nutrients. 2020 Sep 29;12(10):2982. doi: 10.3390/nu12102982.
• Background Zheng X, Qiu Y, Zhong W, Baxter S, Su M, Li Q, Xie G, Ore BM, Qiao S, Spencer MD, Zeisel SH, Zhou Z, Zhao A, Jia W. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids. Metabolomics. 2013 Aug 1;9(4):818-827. doi: 10.1007/s11306-013-0500-6.
• Background Virwani PD, Qian G, Hsu MSS, Pijarnvanit TKKTS, Cheung CN, Chow YH, Tang LK, Tse YH, Xian JW, Lam SS, Lee CPI, Lo CCW, Liu RKC, Ho TL, Chow BY, Leung KS, Tsang HW, Lo EKK, Tung KTS, Chung SK, Yuen MF, Leung SY, Ip P, Hung IF, Louie JCY, El-Nezami H, Ho JWK, Lau KK. Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring. Hypertension. 2023 Jun;80(6):1331-1342. doi: 10.1161/HYPERTENSIONAHA.122.20752. Epub 2023 Apr 19.
• Background Gerdts E, Sudano I, Brouwers S, Borghi C, Bruno RM, Ceconi C, Cornelissen V, Dievart F, Ferrini M, Kahan T, Lochen ML, Maas AHEM, Mahfoud F, Mihailidou AS, Moholdt T, Parati G, de Simone G. Sex differences in arterial hypertension. Eur Heart J. 2022 Dec 7;43(46):4777-4788. doi: 10.1093/eurheartj/ehac470.
• Background Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, Tun HM, Mok CKP, Chau SWH, Tse YK, Cheung CP, Li MKT, Yeung GTY, Cheong PK, Chan FKL, Ng SC. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2024 Mar;24(3):256-265. doi: 10.1016/S1473-3099(23)00685-0. Epub 2023 Dec 7.
• Background Su Q, Liu Q, Zhang L, Xu Z, Liu C, Lu W, Ching JY, Li A, Mak JWY, Lui GCY, Ng SSS, Chow KM, Hui DS, Chan PK, Chan FKL, Ng SC. Antibiotics and probiotics impact gut antimicrobial resistance gene reservoir in COVID-19 patients. Gut Microbes. 2022 Jan-Dec;14(1):2128603. doi: 10.1080/19490976.2022.2128603.
• Background Zhang L, Xu Z, Mak JWY, Chow KM, Lui G, Li TCM, Wong CK, Chan PKS, Ching JYL, Fujiwara Y, Chan FKL, Ng SC. Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study. J Gastroenterol Hepatol. 2022 May;37(5):823-831. doi: 10.1111/jgh.15796. Epub 2022 Mar 2.
• Background Chang BJ, Park SU, Jang YS, Ko SH, Joo NM, Kim SI, Kim CH, Chang DK. Effect of functional yogurt NY-YP901 in improving the trait of metabolic syndrome. Eur J Clin Nutr. 2011 Nov;65(11):1250-5. doi: 10.1038/ejcn.2011.115. Epub 2011 Jun 22.
• Background Savard P, Lamarche B, Paradis ME, Thiboutot H, Laurin E, Roy D. Impact of Bifidobacterium animalis subsp. lactis BB-12 and, Lactobacillus acidophilus LA-5-containing yoghurt, on fecal bacterial counts of healthy adults. Int J Food Microbiol. 2011 Sep 1;149(1):50-7. doi: 10.1016/j.ijfoodmicro.2010.12.026. Epub 2011 Jan 15.
• Background Agerholm-Larsen L, Raben A, Haulrik N, Hansen AS, Manders M, Astrup A. Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur J Clin Nutr. 2000 Apr;54(4):288-97. doi: 10.1038/sj.ejcn.1600937.
• Background Usinger L, Ibsen H, Linneberg A, Azizi M, Flambard B, Jensen LT. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk. Clin Physiol Funct Imaging. 2010 Mar;30(2):162-8. doi: 10.1111/j.1475-097X.2009.00921.x. Epub 2010 Jan 26.
• Background van der Zander K, Jakel M, Bianco V, Koning MM. Fermented lactotripeptides-containing milk lowers daytime blood pressure in high normal-to-mild hypertensive subjects. J Hum Hypertens. 2008 Nov;22(11):804-6. doi: 10.1038/jhh.2008.59. Epub 2008 Jun 5.
• Background Sano J, Ohki K, Higuchi T, Aihara K, Mizuno S, Kajimoto O, Nakagawa S, Kajimoto Y, Nakamura Y. Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. J Med Food. 2005 Winter;8(4):423-30. doi: 10.1089/jmf.2005.8.423.
• Background Jauhiainen T, Vapaatalo H, Poussa T, Kyronpalo S, Rasmussen M, Korpela R. Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Am J Hypertens. 2005 Dec;18(12 Pt 1):1600-5. doi: 10.1016/j.amjhyper.2005.06.006.
• Background Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y. Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J Am Coll Nutr. 2005 Aug;24(4):257-65. doi: 10.1080/07315724.2005.10719473.
• Background Mizuno S, Matsuura K, Gotou T, Nishimura S, Kajimoto O, Yabune M, Kajimoto Y, Yamamoto N. Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension. Br J Nutr. 2005 Jul;94(1):84-91. doi: 10.1079/bjn20051422.
• Background Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr. 1996 Nov;64(5):767-71. doi: 10.1093/ajcn/64.5.767.
• Background Tuomilehto J, Lindstrom J, Hyyrynen J, Korpela R, Karhunen ML, Mikkola L, Jauhiainen T, Seppo L, Nissinen A. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J Hum Hypertens. 2004 Nov;18(11):795-802. doi: 10.1038/sj.jhh.1001745.
• Background Inoue K, Shirai T, Ochiai H, Kasao M, Hayakawa K, Kimura M, Sansawa H. Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives. Eur J Clin Nutr. 2003 Mar;57(3):490-5. doi: 10.1038/sj.ejcn.1601555.
• Background Wong MCS, Zhang L, Ching JYL, Mak JWY, Huang J, Wang S, Mok CKP, Wong A, Chiu OL, Fung YT, Cheong PK, Tun HM, Ng SC, Chan FKL. Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study). Nutrients. 2023 Apr 20;15(8):1982. doi: 10.3390/nu15081982.
• Background Shimada M, Hasegawa T, Nishimura C, Kan H, Kanno T, Nakamura T, Matsubayashi T. Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. Clin Exp Hypertens. 2009 Jun;31(4):342-54. doi: 10.1080/10641960902977908.
• Background Ma P, Li T, Ji F, Wang H, Pang J. Effect of GABA on blood pressure and blood dynamics of anesthetic rats. Int J Clin Exp Med. 2015 Aug 15;8(8):14296-302. eCollection 2015.
• Background Duranti S, Ruiz L, Lugli GA, Tames H, Milani C, Mancabelli L, Mancino W, Longhi G, Carnevali L, Sgoifo A, Margolles A, Ventura M, Ruas-Madiedo P, Turroni F. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep. 2020 Aug 24;10(1):14112. doi: 10.1038/s41598-020-70986-z.
• Background Li Y, He L, Zhao Q, Bo T. Microbial and metabolic profiles of bronchopulmonary dysplasia and therapeutic effects of potential probiotics Limosilactobacillus reuteri and Bifidobacterium bifidum. J Appl Microbiol. 2022 Aug;133(2):908-921. doi: 10.1111/jam.15602. Epub 2022 May 16.
• Background Lu W, Wang Y, Fang Z, Wang H, Zhu J, Zhai Q, Zhao J, Zhang H, Chen W. Bifidobacterium longum CCFM752 prevented hypertension and aortic lesion, improved antioxidative ability, and regulated the gut microbiome in spontaneously hypertensive rats. Food Funct. 2022 Jun 6;13(11):6373-6386. doi: 10.1039/d1fo04446j.
• Background Averina OV, Kovtun AS, Mavletova DA, Ziganshin RH, Danilenko VN, Mihaylova D, Blazheva D, Slavchev A, Brazkova M, Ibrahim SA, Krastanov A. Oxidative Stress Response of Probiotic Strain Bifidobacterium longum subsp. longum GT15. Foods. 2023 Sep 7;12(18):3356. doi: 10.3390/foods12183356.
• Background Fan L, Qi Y, Qu S, Chen X, Li A, Hendi M, Xu C, Wang L, Hou T, Si J, Chen S. B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling. Gut Microbes. 2021 Jan-Dec;13(1):1-17. doi: 10.1080/19490976.2020.1826746.
• Background Chen S, Chen L, Qi Y, Xu J, Ge Q, Fan Y, Chen D, Zhang Y, Wang L, Hou T, Yang X, Xi Y, Si J, Kang L, Wang L. Bifidobacterium adolescentis regulates catalase activity and host metabolism and improves healthspan and lifespan in multiple species. Nat Aging. 2021 Nov;1(11):991-1001. doi: 10.1038/s43587-021-00129-0. Epub 2021 Nov 16.
• Background Bai B, Yang Y, Wang Q, Li M, Tian C, Liu Y, Aung LHH, Li PF, Yu T, Chu XM. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020 Sep 18;11(9):776. doi: 10.1038/s41419-020-02985-x.
• Background Sun HJ, Ren XS, Xiong XQ, Chen YZ, Zhao MX, Wang JJ, Zhou YB, Han Y, Chen Q, Li YH, Kang YM, Zhu GQ. NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension. Cell Death Dis. 2017 Oct 5;8(10):e3074. doi: 10.1038/cddis.2017.470.
• Background Rodrigo R, Gonzalez J, Paoletto F. The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res. 2011 Apr;34(4):431-40. doi: 10.1038/hr.2010.264. Epub 2011 Jan 13.
• Background Montezano AC, Touyz RM. Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies. Ann Med. 2012 Jun;44 Suppl 1:S2-16. doi: 10.3109/07853890.2011.653393.
• Background Zhang Z, Zhao L, Zhou X, Meng X, Zhou X. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Front Immunol. 2023 Jan 10;13:1098725. doi: 10.3389/fimmu.2022.1098725. eCollection 2022.
• Background Joseph TA, Pe'er I. An Introduction to Whole-Metagenome Shotgun Sequencing Studies. Methods Mol Biol. 2021;2243:107-122. doi: 10.1007/978-1-0716-1103-6_6.
• Background Zhao TX, Zhang L, Zhou N, Sun DS, Xie JH, Xu SK. Long-term use of probiotics for the management of office and ambulatory blood pressure: A systematic review and meta-analysis of randomized, controlled trials. Food Sci Nutr. 2022 Sep 20;11(1):101-113. doi: 10.1002/fsn3.3069. eCollection 2023 Jan.
• Background Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension. 2014 Oct;64(4):897-903. doi: 10.1161/HYPERTENSIONAHA.114.03469. Epub 2014 Jul 21.
• Background Dong JY, Szeto IM, Makinen K, Gao Q, Wang J, Qin LQ, Zhao Y. Effect of probiotic fermented milk on blood pressure: a meta-analysis of randomised controlled trials. Br J Nutr. 2013 Oct;110(7):1188-94. doi: 10.1017/S0007114513001712. Epub 2013 Jul 3.
• Background Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017 Feb 1;5(1):14. doi: 10.1186/s40168-016-0222-x.
• Background Muralitharan RR, Jama HA, Xie L, Peh A, Snelson M, Marques FZ. Microbial Peer Pressure: The Role of the Gut Microbiota in Hypertension and Its Complications. Hypertension. 2020 Dec;76(6):1674-1687. doi: 10.1161/HYPERTENSIONAHA.120.14473. Epub 2020 Oct 5.
• Background Hamrahian SM, Maarouf OH, Fulop T. A Critical Review of Medication Adherence in Hypertension: Barriers and Facilitators Clinicians Should Consider. Patient Prefer Adherence. 2022 Oct 7;16:2749-2757. doi: 10.2147/PPA.S368784. eCollection 2022.

Drugs

Indications